identifier: traitmech:000088 label: antibiotic resistance definition: A physiological capacity to grow in the presence of antibiotic concentrations that inhibit susceptible cells, mediated by efflux, target modification, drug inactivation, or reduced permeability. definition_source: DOI:10.1038/nrmicro3380 trait_category: PHYSIOLOGY term_kind: CLASS mapping_status: REVIEWED parent_traits: - METPO:1000059 synonyms: - synonym_text: antimicrobial resistance synonym_type: RELATED_SYNONYM source: DOI:10.1038/nrmicro3380 evidence: - reference: DOI:10.1038/nrmicro3380 notes: Blair et al. review the molecular mechanisms of antibiotic resistance (efflux, target alteration, drug inactivation, reduced uptake). - reference: DOI:10.1038/s41579-022-00820-y notes: Updated review revisits molecular mechanisms of antibiotic resistance. canonical_examples: - taxon_id: NCBITaxon:1280 taxon_label: Staphylococcus aureus note: "Iconic antibiotic-resistance organism (MRSA; methicillin/multidrug resistance)." reference: PMID:11418146 causal_graphs: - graph_id: antibiotic_resistance_mechanisms title: Mechanisms of antibiotic resistance description: Evidence-backed causal sketch linking resistance determinants (efflux, target modification, drug inactivation) to growth under antibiotic exposure. nodes: - node_id: antibiotic_resistance_trait label: antibiotic resistance node_type: TRAIT grounding: traitmech:000088 description: Capacity to grow despite inhibitory antibiotic concentrations. - node_id: efflux_pump label: drug efflux pump node_type: GENE_OR_PROTEIN description: Transporter that expels antibiotics from the cell. grounding: UniProtKB:A3RNR9 - node_id: antibiotic_response_process label: response to antibiotic node_type: BIOLOGICAL_PROCESS grounding: GO:0046677 description: Cellular response conferring survival under antibiotic exposure. - node_id: intracellular_antibiotic_concentration label: intracellular antibiotic concentration node_type: CHEMICAL description: Concentration of antibiotic accumulated inside the cell. - node_id: outer_membrane_porin label: outer membrane porin node_type: GENE_OR_PROTEIN description: Outer-membrane channel mediating antibiotic influx; loss/modification reduces permeability. grounding: UniProtKB:A0A024EG85 - node_id: antibiotic_influx label: antibiotic influx node_type: BIOLOGICAL_PROCESS description: Uptake of antibiotic across the cell envelope. - node_id: beta_lactamase label: beta-lactamase node_type: GENE_OR_PROTEIN description: Enzyme that hydrolyzes the beta-lactam ring, inactivating beta-lactam antibiotics. grounding: UniProtKB:A0A059L9H0 - node_id: beta_lactam_antibiotic label: beta-lactam antibiotic node_type: CHEMICAL description: Antibiotic class containing a beta-lactam ring. grounding: CHEBI:27933 - node_id: qrdr_mutation label: QRDR mutation in DNA gyrase/topoisomerase IV node_type: GENE_OR_PROTEIN description: Quinolone resistance-determining region mutation altering the fluoroquinolone target. - node_id: fluoroquinolone label: fluoroquinolone node_type: CHEMICAL description: Fluoroquinolone class antibiotic targeting DNA gyrase/topoisomerase IV. - node_id: rrna_methylation_23s label: 23S rRNA methylation node_type: BIOLOGICAL_PROCESS description: Methylation of 23S rRNA that modifies the ribosomal antibiotic-binding site. - node_id: macrolide_antibiotic label: macrolide antibiotic node_type: CHEMICAL description: Macrolide class antibiotic binding the 23S rRNA of the large ribosomal subunit. grounding: CHEBI:25105 edges: - subject: efflux_pump predicate: enables object: antibiotic_resistance_trait description: Drug efflux is one determinant enabling resistance. evidence: - reference: DOI:10.1038/nrmicro3380 notes: Blair et al. review efflux among resistance mechanisms. predicate_id: RO:0002327 - subject: antibiotic_resistance_trait predicate: participates in object: antibiotic_response_process description: Resistance is part of the cellular response to antibiotics. evidence: - reference: DOI:10.1038/s41579-022-00820-y notes: Updated review of antibiotic-resistance mechanisms. predicate_id: biolink:participates_in - subject: efflux_pump predicate: decreases object: intracellular_antibiotic_concentration description: Efflux pump overexpression lowers intracellular antibiotic concentration, producing resistance phenotypes. evidence: - reference: DOI:10.3390/pharmaceutics16020170 notes: Efflux pumps reduce intracellular antibiotic concentrations; upregulation under antibiotic exposure produces resistance phenotypes (broad across Gram-positive/negative). predicate_id: RO:0002212 - subject: outer_membrane_porin predicate: decreases object: antibiotic_influx description: Porin loss/modification reduces antibiotic influx, a major resistance mechanism. evidence: - reference: DOI:10.3390/pharmaceutics16020170 notes: Reduced permeability/porin loss and modification of outer membrane porin channels listed as major resistance mechanisms. predicate_id: RO:0002212 - subject: beta_lactamase predicate: hydrolyzes object: beta_lactam_antibiotic description: Beta-lactamases hydrolyze the beta-lactam ring, inactivating the drug. evidence: - reference: DOI:10.1038/s43856-024-00591-y notes: Drug hydrolysis by beta-lactamases; beta-lactamases hydrolyze the beta-lactam ring. Strong canonical mechanism. predicate_id: METPO:2000013 - subject: qrdr_mutation predicate: confers resistance to object: fluoroquinolone description: QRDR mutations in DNA gyrase/topoisomerase IV confer fluoroquinolone resistance (class-level edge). evidence: - reference: DOI:10.3389/fphar.2024.1444781 notes: QRDR mutations in DNA gyrase and topoisomerase IV cause quinolone/fluoroquinolone resistance. - subject: rrna_methylation_23s predicate: decreases binding of object: macrolide_antibiotic description: 23S rRNA methylation modifies the ribosomal target, decreasing macrolide binding and conferring resistance. evidence: - reference: DOI:10.3389/fphar.2024.1444781 notes: Methylation of 23S rRNA confers linezolid, chloramphenicol, clindamycin, and macrolide resistance. curation_history: - timestamp: '2026-06-04T00:00:00Z' curator: claude action: PROPOSED_FROM_RESEARCH changes: Proposed candidate PHYSIOLOGY trait (antibiotic resistance) from literature research. Distinct from persister-cell tolerance (non-genetic). llm_assisted: true - timestamp: '2026-06-08T13:00:00Z' curator: claude action: CURATED_CAUSAL_GRAPH changes: Added evidence-backed causal graph (resistance mechanisms) with GO node grounding and RO/biolink predicate groundings; promoted PROPOSED to REVIEWED. llm_assisted: true - timestamp: '2026-06-14T06:38:15Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A3RNR9×1). llm_assisted: true - timestamp: '2026-06-23T00:00:00Z' curator: claude action: ENRICH_CAUSAL_GRAPH changes: Added 5 evidence-backed generic edges (9 new nodes) from the deep-research report. llm_assisted: true - timestamp: '2026-06-24T17:21:14Z' curator: claude action: GROUND_CAUSAL_PREDICATES changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002212×2). llm_assisted: true - timestamp: '2026-06-24T17:23:34Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:27933×1, CHEBI:25105×1). llm_assisted: true - timestamp: '2026-06-24T17:23:39Z' curator: claude action: GROUND_CAUSAL_PREDICATES changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000013×1). llm_assisted: true - timestamp: '2026-06-26T07:15:20Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A024EG85×1, UniProtKB:A0A059L9H0×1). llm_assisted: true